rs1557043736

Variant names:

• chrX-153688592-C-G
• rs1557043736
• NM_005629.4:c.18C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-153688592-C-G
• chrX-153688592-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_005629.4(SLC6A8):​c.18C>G​(p.Ala6Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000422 in 947,071 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A6A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000042 (0 hom. 1 hem.)
• Consequence: SLC6A8 NM_005629.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: -2.10
• Publications: 0 publications found

Genes affected

SLC6A8 (HGNC:11055): (solute carrier family 6 member 8) The protein encoded by this gene is a plasma membrane protein whose function is to transport creatine into and out of cells. Defects in this gene can result in X-linked creatine deficiency syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

PNCK (HGNC:13415): (pregnancy up-regulated nonubiquitous CaM kinase) PNCK is a member of the calcium/calmodulin-dependent protein kinase family of protein serine/threonine kinases (see CAMK1; MIM 604998) (Gardner et al., 2000 [PubMed 10673339]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant X-153688592-C-G is Benign according to our data. Variant chrX-153688592-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1615354.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.1 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	NM_005629.4	MANE Select	c.18C>G	p.Ala6Ala	synonymous	Exon 1 of 13	NP_005620.1	P48029-1
	SLC6A8	NM_001142805.2		c.18C>G	p.Ala6Ala	synonymous	Exon 1 of 13	NP_001136277.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A8	ENST00000253122.10	TSL:1 MANE Select	c.18C>G	p.Ala6Ala	synonymous	Exon 1 of 13	ENSP00000253122.5	P48029-1
	SLC6A8	ENST00000955775.1		c.18C>G	p.Ala6Ala	synonymous	Exon 1 of 13	ENSP00000625834.1
	SLC6A8	ENST00000922630.1		c.18C>G	p.Ala6Ala	synonymous	Exon 1 of 13	ENSP00000592689.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD2 exomes AF: 0.0000180 AC: 1 AN: 55460 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.00000422 AC: 4 AN: 947071 Hom.: 0 Cov.: 24 AF XY: 0.00000332 AC XY: 1 AN XY: 300969

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 19378

American (AMR) AF: 0.00 AC: 0 AN: 17915

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15115

East Asian (EAS) AF: 0.00 AC: 0 AN: 18297

South Asian (SAS) AF: 0.00 AC: 0 AN: 41492

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31822

Middle Eastern (MID) AF: 0.000405 AC: 1 AN: 2472

European-Non Finnish (NFE) AF: 0.00000393 AC: 3 AN: 762604

Other (OTH) AF: 0.00 AC: 0 AN: 37976

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00131091), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 20

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Creatine deficiency syndrome 1 (1)
-	-	1	Creatine transporter deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		-2.1
PromoterAI		-0.030	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1557043736; hg19: chrX-152954047;